DAGL-Beta Functions as a PUFA-Specific Triacylglycerol Lipase in Macrophages

Cell Chem Biol. 2020 Mar 19;27(3):314-321.e5. doi: 10.1016/j.chembiol.2020.01.005. Epub 2020 Jan 27.

Abstract

Here, we apply quantitative chemical proteomics and untargeted lipidomics to assign a polyunsaturated fatty acid (PUFA)-specific triacylglycerol (TAG) lipase activity for diacylglycerol lipase-beta (DAGLβ) in macrophages. We demonstrate that DAGLβ but not DAGLα is expressed and active in bone marrow-derived macrophages (BMDMs) as determined by activity-based protein profiling analysis of SILAC BMDMs. Genetic disruption of DAGLβ resulted in accumulation of cellular TAGs composed of PUFA but not saturated/low unsaturated fatty acid counterparts, which is recapitulated in wild-type macrophages treated with a DAGLβ-selective inhibitor. Biochemical assays with synthetic substrates confirm PUFA-TAGs as authentic DAGLβ substrates. In summary, our findings identify DAGLβ as a PUFA-specific TAG lipase in primary macrophages.

Keywords: 2-arachidonoylglycerol; TAG lipase; activity-based protein profiling; adipose triglyceride; chemical proteomics; diacylglycerol; diacylglycerol lipase; endocannabinoid; inflammation; lipidomics; lipolysis; macrophage; triglyceride.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Chromatography, Liquid
  • Fatty Acids, Unsaturated / chemistry
  • Fatty Acids, Unsaturated / metabolism*
  • Lipase / chemistry
  • Lipase / metabolism*
  • Lipoprotein Lipase / chemistry
  • Lipoprotein Lipase / metabolism*
  • Macrophages / metabolism*
  • Mass Spectrometry
  • Metabolomics
  • Mice

Substances

  • Fatty Acids, Unsaturated
  • Lipase
  • Lipoprotein Lipase
  • diacylglycerol lipase beta, mouse